tbuckley/cabot-search huggingface dataset:
Obesity Is Associated with Altered Tumor Metabolism in Metastatic Melanoma
Authors: Andrew W. Hahn, Ashley V. Menk, Dayana B. Rivadeneira, Ryan C. Augustin, Mingchu Xu, Jun Li, Xiaogang Wu, Aditya K. Mishra, Tuba N. Gide, Camelia Quek, Yan Zang, Christine N. Spencer, Alexander M. Menzies, Carrie R. Daniel, Courtney W. Hudgens, Theodore Nowicki, Lauren E. Haydu, M.A. Wadud Khan, Vancheswaran Gopalakrishnan, Elizabeth M. Burton, Jared Malke, Julie M. Simon, Chantale Bernatchez, Nagireddy Putluri, Scott E. Woodman, Y.N. Vashisht Gopal, Renato Guerrieri, Grant M. Fischer, Jian Wang, Khalida M. Wani, John F. Thompson, Jeffrey E. Lee, Patrick Hwu, Nadim Ajami, Jeffrey E. Gershenwald, Georgina V. Long, Richard A. Scolyer, Michael T. Tetzlaff, Alexander J. Lazar, Dirk Schadendorf, Jennifer A. Wargo, John M. Kirkwood, Ralph J. DeBerardinis, Han Liang, Andrew Futreal, Jianhua Zhang, James S. Wilmott, Weiyi Peng, Michael A. Davies, Greg M. Delgoffe, Yana G. Najjar, Jennifer L. McQuade
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Overweight/obese (OW/OB) patients with metastatic melanoma unexpectedly have improved outcomes with immune checkpoint inhibitors (ICI) and BRAF-targeted therapies. The mechanism(s) underlying this association remain unclear, thus we assessed the integrated molecular, metabolic, and immune profile of tumors, as well as gut microbiome features, for associations with patient body mass index (BMI). Experimental Design: Associations between BMI [normal (NL &amp;lt; 25) or OW/OB (BMI ≥ 25)] and tumor or microbiome characteristics were examined in specimens from 782 patients with metastatic melanoma across 7 cohorts. DNA associations were evaluated in The Cancer Genome Atlas cohort. RNA sequencing from 4 cohorts (n = 357) was batch corrected and gene set enrichment analysis (GSEA) by BMI category was performed. Metabolic profiling was conducted in a subset of patients (x = 36) by LC/MS, and in flow-sorted melanoma tumor cells (x = 37) and patient-derived melanoma cell lines (x = 17) using the Seahorse XF assay. Gut microbiome features were examined in an independent cohort (n = 371). Results: DNA mutations and copy number variations were not associated with BMI. GSEA demonstrated that tumors from OW/OB patients were metabolically quiescent, with downregulation of oxidative phosphorylation and multiple other metabolic pathways. Direct metabolite analysis and functional metabolic profiling confirmed decreased central carbon metabolism in OW/OB metastatic melanoma tumors and patient-derived cell lines. The overall structure, diversity, and taxonomy of the fecal microbiome did not differ by BMI. Conclusions: These findings suggest that the host metabolic phenotype influences melanoma metabolism and provide insight into the improved outcomes observed in OW/OB patients with metastatic melanoma treated with ICIs and targeted therapies. See related commentary by Smalley, p. 5
Screening for Syphilis in Nonpregnant Adults and Adolescents
Authors: Ronnie M. Gravett, Jeanne Marrazzo
Journal: JAMA Network Open (2022)

US Preventive Services Task Force; Carol M. Mangione, MD, MSPH; Michael J. Barry, MD; Wanda K. Nicholson, MD, MPH, MBA; Michael Cabana, MD, MA, MPH; David Chelmow, MD; Tumaini Rucker Coker, MD, MBA; Esa M. Davis, MD, MPH; Katrina E. Donahue, MD, MPH; Carlos Roberto Jaén, MD, PhD, MS; Martha Kubik, PhD, RN; Li Li, MD, PhD, MPH; Gbenga Ogedegbe, MD, MPH; Lori Pbert, PhD; John M. Ruiz, PhD; James Stevermer, MD, MSPH; John B. Wong, MD
Long-term Protection Associated With COVID-19 Vaccination and Prior Infection
Authors: Mark W. Tenforde, Ruth Link-Gelles, Manish M. Patel
Journal: JAMA (2022)

Dan-Yu Lin, PhD; Yu Gu, BS; Yangjianchen Xu, BS; Bradford Wheeler, MPH; Hayley Young, MPH; Shadia Khan Sunny, MD, PhD; Zack Moore, MD; Donglin Zeng, PhD
Screening for Syphilis Infection in Nonpregnant Adults and Adolescents
Authors: Michelle L. Henninger, Sarah I. Bean, Jennifer S. Lin
Journal: JAMA (2022)

This systematic review to support the 2022 US Preventive Services Task Force Recommendation Statement on screening for syphilis infection summarizes published evidence on the benefits and harms of screening for syphilis infection in asymptomatic, nonpregnant adults and adolescents at increased risk for syphilis infection.
Novel Lymphocyte-Independent Antitumor Activity by PD-1 Blocking Antibody against PD-1+ Chemoresistant Lung Cancer Cells
Authors: Ramona Rotolo, Valeria Leuci, Chiara Donini, Federica Galvagno, Annamaria Massa, Maria Chiara De Santis, Serena Peirone, Giovanni Medico, Martina Sanlorenzo, Igor Vujic, Loretta Gammaitoni, Marco Basiricò, Luisella Righi, Chiara Riganti, Iris Chiara Salaroglio, Francesca Napoli, Fabrizio Tabbò, Annapaola Mariniello, Elisa Vigna, Chiara Modica, Lorenzo D’Ambrosio, Giovanni Grignani, Riccardo Taulli, Emilio Hirsch, Matteo Cereda, Massimo Aglietta, Giorgio Vittorio Scagliotti, Silvia Novello, Paolo Bironzo, Dario Sangiolo
Journal: Clinical Cancer Research (2022)

Abstract Purpose: Antibodies against the lymphocyte PD-1 (aPD-1) receptor are cornerstone agents for advanced non–small cell lung cancer (NSCLC), based on their ability to restore the exhausted antitumor immune response. Our study reports a novel, lymphocyte-independent, therapeutic activity of aPD-1 against NSCLC, blocking the tumor-intrinsic PD-1 receptors on chemoresistant cells. Experimental Design: PD-1 in NSCLC cells was explored in vitro at baseline, including stem-like pneumospheres, and following treatment with cisplatin both at transcriptional and protein levels. PD-1 signaling and RNA sequencing were assessed. The lymphocyte-independent antitumor activity of aPD-1 was explored in vitro, by PD-1 blockade and stimulation with soluble ligand (PD-L1s), and in vivo within NSCLC xenograft models. Results: We showed the existence of PD-1+ NSCLC cell subsets in cell lines and large in silico datasets (Cancer Cell Line Encyclopedia and The Cancer Genome Atlas). Cisplatin significantly increased PD-1 expression on chemo-surviving NSCLC cells (2.5-fold P = 0.0014), while the sequential treatment with anti–PD-1 Ab impaired their recovery after chemotherapy. PD-1 was found to be associated with tumor stemness features. PD-1 expression was enhanced in NSCLC stem-like pneumospheres (P &amp;lt; 0.0001), significantly promoted by stimulation with soluble PD-L1 (+27% ± 4, P &amp;lt; 0.0001) and inhibited by PD-1 blockade (−30% ± 3, P &amp;lt; 0.0001). The intravenous monotherapy with anti–PD-1 significantly inhibited tumor growth of NSCLC xenografts in immunodeficient mice, without the contribution of the immune system, and delayed the occurrence of chemoresistance when combined with cisplatin. Conclusions: We report first evidence of a novel lymphocyte-independent activity of anti–PD-1 antibodies in NSCLC, capable of inhibiting chemo-surviving NSCLC cells and exploitable to contrast disease relapses following chemotherapy. See related commentary by Augustin et al., p. 505
Ischemic Stroke in Patients With Asymptomatic Severe Carotid Stenosis Without Surgical Intervention—Reply
Authors: Robert W. Chang, Mai N. Nguyen-Huynh, Andrew L. Avins
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Corrigendum to “Remodeling tumor immunosuppressive microenvironment via a novel bioactive nanovaccines potentiates the efficacy of cancer immunotherapy” [Bioactive Mater. 16 107–119]
Authors: Xiaoxue Xie, Yi Feng, Hanxi Zhang, Qingqing Su, Ting Song, Geng Yang, Ningxi Li, Xiaodan Wei, Tingting Li, Xiang Qin, Shun Li, Chunhui Wu, Xiaojuan Zhang, Guixue Wang, Yiyao Liu, Hong Yang
Journal: Bioactive Materials (2022)

[This corrects the article DOI: 10.1016/j.bioactmat.2022.03.008.].
Screening for Syphilis Infection in Nonpregnant Adolescents and Adults
Authors: Carol M. Mangione, Michael J. Barry, Wanda K. Nicholson, Michael Cabana, David Chelmow, Tumaini Rucker Coker, Esa M. Davis, Katrina E. Donahue, Carlos Roberto Jaén, Martha Kubik, Li Li, Gbenga Ogedegbe, Lori Pbert, John M. Ruiz, James Stevermer, John B. Wong
Journal: JAMA (2022)

Importance Syphilis is a sexually transmitted infection that can progress through different stages (primary, secondary, latent, and tertiary) and cause serious health problems if left untreated. Reported cases of primary and secondary syphilis in the US increased from a record low of 2.1 cases per 100 000 population in 2000 and 2001 to 11.9 cases per 100 000 population in 2019. Men account for the majority of cases (83% of primary and secondary syphilis cases in 2019), and rates among women nearly tripled from 2015 to 2019. Objective To reaffirm its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence update focusing on targeted key questions evaluating the performance of risk assessment tools and the benefits and harms of screening for syphilis in nonpregnant adolescents and adults. Population Asymptomatic, nonpregnant adolescents and adults who have ever been sexually active and are at increased risk for syphilis infection. Evidence Assessment Using a reaffirmation process, the USPSTF concludes with high certainty that there is a substantial net benefit of screening for syphilis infection in nonpregnant persons who are at increased risk for infection. Recommendation The USPSTF recommends screening for syphilis infection in persons who are at increased risk for infection. (A recommendation)
Letter to the Editor: Questioning the existence of Aif1 +, Csf1r + mesenchymal stem cells
Authors: David A. Hume
Journal: Hepatology (2022)

1Mater Research Institute‐University of Queensland, Translational Research InstituteBrisbane Queensland Australia *Correspondence David A. Hume, Mater Research Institute‐University of Queensland, Translational Research Institute, Brisbane, QLD, Australia. Email: [email protected]
A Novel B7-H6–Targeted IgG-Like T Cell–Engaging Antibody for the Treatment of Gastrointestinal Tumors
Authors: Wei Zhang, Aurélie Auguste, Xiaoyun Liao, Christian Walterskirchen, Kathrin Bauer, Yu-Hsi Lin, Ling Yang, Farzaneh Sayedian, Markus Fabits, Michael Bergmann, Carina Binder, Leticia Corrales, Anne B. Vogt, Lindsey J. Hudson, Martin P. Barnes, Arnima Bisht, Craig Giragossian, Vladimir Voynov, Paul J. Adam, Susanne Hipp
Journal: Clinical Cancer Research (2022)

Advanced-stage gastrointestinal cancers represent a high unmet need requiring new effective therapies. We investigated the antitumor activity of a novel T cell-engaging antibody (B7-H6/CD3 ITE) targeting B7-H6, a tumor-associated antigen that is expressed in gastrointestinal tumors.Membrane proteomics and IHC analysis identified B7-H6 as a tumor-associated antigen in gastrointestinal tumor tissues with no to very little expression in normal tissues. The antitumor activity and mode of action of B7-H6/CD3 ITE was evaluated in in vitro coculture assays, in humanized mouse tumor models, and in colorectal cancer precision cut tumor slice cultures.B7-H6 expression was detected in 98% of colorectal cancer, 77% of gastric cancer, and 63% of pancreatic cancer tissue samples. B7-H6/CD3 ITE-mediated redirection of T cells toward B7-H6-positive tumor cells resulted in B7-H6-dependent lysis of tumor cells, activation and proliferation of T cells, and cytokine secretion in in vitro coculture assays, and infiltration of T cells into tumor tissues associated with tumor regression in in vivo colorectal cancer models. In primary patient-derived colorectal cancer precision-cut tumor slice cultures, treatment with B7-H6/CD3 ITE elicited cytokine secretion by endogenous tumor-infiltrating immune cells. Combination with anti-PD-1 further enhanced the activity of the B7-H6/CD3 ITE.These data highlight the potential of the B7-H6/CD3 ITE to induce T cell-redirected lysis of tumor cells and recruitment of T cells into noninflamed tumor tissues, leading to antitumor activity in in vitro, in vivo, and human tumor slice cultures, which supports further evaluation in a clinical study.
Altered microbial biogeography in an innate model of colitis
Authors: Antonia Boger-May, Theodore Reed, Diana LaTorre, Katelyn Ruley-Haase, Hunter Hoffman, Lauren English, Connor Roncagli, Anne-Marie Overstreet, David Boone
Journal: Gut Microbes (2022)

Changes in the spatial organization, or biogeography, of colonic microbes have been observed in human inflammatory bowel disease (IBD) and mouse models of IBD. We have developed a mouse model of IBD that occurs spontaneously and consistently in the absence of adaptive immunity. Mice expressing tumor necrosis factor-induced protein 3 (TNFAIP3) in intestinal epithelial cells (villin-TNFAIP3) develop colitis when interbred with Recombination Activating 1-deficient mice (RAG1−/−). The colitis in villin-TNFAIP3 × RAG1−/− (TRAG) mice is prevented by antibiotics, indicating a role for microbes in this innate colitis. We therefore explored the biogeography of microbes and responses to antibiotics in TRAG colitis. Laser capture microdissection and 16S rRNA sequencing revealed altered microbial populations across the transverse axis of the colon as the inner mucus layer of TRAG, but not RAG1−/−, mice was infiltrated by microbes, which included increased abundance of the classes Gammaproteobacteria and Actinobacteria. Along the longitudinal axis differences in the efficacy of antibiotics to prevent colitis were evident. Neomycin was most effective for prevention of inflammation in the cecum, while ampicillin was most effective in the proximal and distal colon. RAG1−/−, but not TRAG, mice exhibited a structured pattern of bacterial abundance with decreased Firmicutes and Proteobacteria but increased Bacteroidetes along the proximal to distal axis of the gut. TRAG mice exhibited increased relative abundance of potential pathobionts including Bifidobacterium animalis along the longitudinal axis of the gut whereas others, like Helicobacter hepaticus were increased only in the cecum. Potential beneficial organisms including Roseburia were decreased in the proximal regions of the TRAG colon, while Bifidobacterium pseudolongulum was decreased in the TRAG distal colon. Thus, the innate immune system maintains a structured, spatially organized, gut microbiome along the transverse and longitudinal axis of the gut, and disruption of this biogeography is a feature of innate immune colitis.
Melatonin inhibits ESCC tumor growth by mitigating the HDAC7/β-catenin/c-Myc positive feedback loop and suppressing the USP10-maintained HDAC7 protein stability
Authors: Zhi-Qiang Ma, Ying-Tong Feng, Kai Guo, Dong Liu, Chang-Jian Shao, Ming-Hong Pan, Yi-Meng Zhang, Yu-Xi Zhang, Di Lu, Di Huang, Fan Zhang, Jin-Liang Wang, Bo Yang, Jing Han, Xiao-Long Yan, Yi Hu
Journal: Military Medical Research (2022)

Melatonin, a natural hormone secreted by the pineal gland, has been reported to exhibit antitumor properties through diverse mechanisms of action. However, the oncostatic function of melatonin on esophageal squamous cell carcinoma (ESCC) remains elusive. This study was conducted to investigate the potential effect and underlying molecular mechanism of melatonin as single anticancer agent against ESCC cells.ESCC cell lines treated with or without melatonin were used in this study. In vitro colony formation and EdU incorporation assays, and nude mice tumor xenograft model were used to confirm the proliferative capacities of ESCC cells. RNA-seq, qPCR, Western blotting, recombinant lentivirus-mediated target gene overexpression or knockdown, plasmids transfection and co-IP were applied to investigate the underlying molecular mechanism by which melatonin inhibited ESCC cell growth. IHC staining on ESCC tissue microarray and further survival analyses were performed to explore the relationship between target genes' expression and prognosis of ESCC.Melatonin treatment dose-dependently inhibited the proliferative ability and the expression of histone deacetylase 7 (HDAC7), c-Myc and ubiquitin-specific peptidase 10 (USP10) in ESCC cells (P < 0.05). The expressions of HDAC7, c-Myc and USP10 in tumors were detected significantly higher than the paired normal tissues from 148 ESCC patients (P < 0.001). Then, the Kaplan-Meier survival analyses suggested that ESCC patients with high HDAC7, c-Myc or USP10 levels predicted worse overall survival (Log-rank P < 0.001). Co-IP and Western blotting analyses further revealed that HDAC7 physically deacetylated and activated β-catenin thus promoting downstream target c-Myc gene transcription. Notably, our mechanistic study validated that HDAC7/β-catenin/c-Myc could form the positive feedback loop to enhance ESCC cell growth, and USP10 could deubiquitinate and stabilize HDAC7 protein in the ESCC cells. Additionally, we verified that inhibition of the HDAC7/β-catenin/c-Myc axis and USP10/HDAC7 pathway mediated the anti-proliferative action of melatonin on ESCC cells.Our findings elucidate that melatonin mitigates the HDAC7/β-catenin/c-Myc positive feedback loop and inhibits the USP10-maintained HDAC7 protein stability thus suppressing ESCC cell growth, and provides the reference for identifying biomarkers and therapeutic targets for ESCC.
Foreign Letters
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Left Ventricular Assist Devices in Advanced Heart Failure
Authors: Mark H. Drazner
Journal: JAMA (2022)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Magnetic Nanodroplets for Enhanced Deep Penetration of Solid Tumors and Simultaneous Magnetothermal‐Sensitized Immunotherapy against Tumor Proliferation and Metastasis
Authors: Junrui Wang, Wenli Zhang, Zhuoyan Xie, Xingyue Wang, Ying Luo, Weixi Jiang, Yun Liu, Zhigang Wang, Haitao Ran, Weixiang Song, Dajing Guo
Journal: Advanced Healthcare Materials (2022)

The central cells of solid tumors are more proliferative and metastatic than the marginal cells. Therefore, more intelligent strategies for targeting cells with deep spatial distributions in solid tumors remain to be explored. In this work, a biocompatible nanotheranostic agent with a lipid membrane-coated, Fe3 O4 and perfluoropentane (PFP)-loaded, cRGD peptide (specifically targeting the integrin αvβ3 receptor)-grafted, magnetic nanodroplets (MNDs) is developed. The MNDs exhibit excellent magnetothermal conversion and controllable magnetic hyperthermia (MHT) through alternating magnetic field regulation. Furthermore, MHT-mediated magnetic droplet vaporization (MDV) induces the expansion of the MNDs to transform them into ultrasonic microbubbles, increasing the permeability of tissue and the cell membrane via the ultrasound-targeted microbubble destruction (UTMD) technique and thereby promoting the deep penetration of MNDs in solid tumors. More importantly, MHT not only causes apoptotic damage by downregulating the expression of the HSP70, cyclin D1, and Bcl-2 proteins in tumor cells but also improves the response rate to T-cell-related immunotherapy by upregulating PD-L1 expression in tumor cells, thus inhibiting the growth of both primary and metastatic tumors. Overall, this work introduces a distinct application of nanoultrasonic biomedicine in cancer therapy and provides an attractive immunotherapy strategy for preventing the proliferation and metastasis of deeply distributed cells in solid tumors.